High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Purpose: Orthodontic tooth movement occurs during the bone remodeling induced by therapeutic mechanical strain. It is important to investigate the relation between the strength of mechanical stress and bone formation activity. The aim of this study was to determine the effect of high-magnitude mechanical strain on bone formation in detail.

Materials and methods: Osteoblast-like cells isolated from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48?h. To phenotypically investigate the effect of TF, we measured the number and the size of bone nodules stained by von Kossa technique on day 21 after cell seeding and determined the calcium content of bone nodules on day 14. Furthermore, we examined the gene expression of BMP-2, Runx2 and Msx2, which are important factors for bone nodule formation, on days 1, 4 and 7 after TF loading.

Results: The maximum bone nodule size in the control group was 1620 and 719?μm in the TF group. Furthermore, the mean number of bone nodules sized over 360?μm in the TF group was significantly decreased compared to the control group. The calcium content was also significantly decreased to 42% by TF loading. The mRNA expression of BMP-2, Runx2 and Msx2 was decreased 1 and 4 days after TF loading.

Conclusion: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.     

Pouchitis--recurrence of the inflammatory bowel disease?

The incidence and characteristics of reservoir inflammation after restorative proctocolectomy for ulcerative colitis were studied in a series of 179 patients. The median follow up time was 27 months (range 6-80). Pouchitis occurred in 36 patients (20%) and nine of these (5%) developed a chronic, persisting pouchitis. There were no pouch failures as a result of pouchitis and no significant adverse effect on longterm functional outcome. The overall cumulative risk to develop pouchitis four years after surgery was 23%. The risk of pouchitis is unpredictable on clinical grounds except that there were significantly less patients with left sided colitis in the group who subsequently developed pouchitis. Morphological and histochemical studies showed a greater degree of colonic metaplasia in the pouch mucosa in patients with pouchitis and patients with a chronic pouchitis had the highest degree of changes. The results support the view that pouchitis is a novel manifestation of inflammatory bowel disease in ileal mucosa that has changed slowly to a colon like mucosa.     

Changes in microtubule-associated protein-2 (MAP2) expression during development and after status epilepticus in the immature rat hippocampus

In this study, we analyzed the spatiotemporal expression patterns of the high-molecular weight (MAP2a and b) and low-molecular weight (MAP2c and d) cytoskeletal microtubule-associated protein-2 (MAP2) isoforms with Western blotting, and the cellular localization of the high-molecular weight MAP2 isoforms with immunocytochemistry in the hippocampi of 1- to 21-day-old rats. Moreover, the temporal profile (from 30 min to 1 week) of MAP2 isoform reactivity to kainic acid-induced status epilepticus was studied in P9 rats. During development, the expression of the high-molecular weight MAP2 isoforms significantly increased, while the low-molecular weight isoforms decreased, the most prominent changes occurring during the second postnatal week. This developmental increase in the high-molecular weight MAP2 expression was also confirmed with immunocytochemistry, which showed increased immunoreactivity, particularly in the molecular layers of the dentate gyrus, and in CA1 and CA3 stratum radiatum. In 9-day-old rats, status epilepticus resulted in a rapid transient increase (about 210%) in the high-molecular weight MAP2 expression, without any effect on the low-molecular weight MAP2. Moreover, disturbed dendritic structure in the CA1 and CA3 stratum radiatum was manifested as formation of varicosities 3h after the kainic acid treatment. The strictly developmentally regulated MAP2 isoform expression suggests different functional roles for these proteins during the postnatal development in the rat hippocampus. Moreover, high-molecular weight MAP2s may play a role in nerve cell survival during cell stress.     

Molecular epidemiology of an outbreak caused by methicillin-resistant Staphylococcus aureus in a health care ward and associated nursing home

Our point-prevalence survey followed an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a long-term care facility and identified five MRSA strains, of which two possessed an outbreak genotype not encountered previously and three had another profile. All of them possessed SCCmec type V. Six methicillin-sensitive S. aureus strains were genotypically related to the epidemic strains.     

Pets, parental atopy, and asthma in adults

BACKGROUND: Studies of exposure to pets and the risk of asthma have provided conflicting results. OBJECTIVE: We conducted a population-based incident case-control study to assess the relationship of current and previous pet keeping with the risk of adult-onset asthma. We also investigated whether genetic propensity as a result of parental atopy modifies these relations. METHODS: From the source population of 441,000 inhabitants of a geographically defined area in South Finland, we systematically recruited, during a 2.5-year period, all new cases of asthma in 21- to 63-year-old adults and randomly selected control subjects. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and a control series of 932 control subjects. Information on current and past exposure to hairy pets was collected by using a self-administered questionnaire. RESULTS: In logistic regression analysis the risk of asthma was lower among subjects with pets during the past 12 months (adjusted odds ratio [OR], 0.74; 95% confidence interval [CI], 0.57-0.96) but higher among subjects with pets more than 12 months previously (adjusted OR, 1.39; 95% CI, 1.05-1.84). Parental atopy increased the risk of asthma (OR, 1.88; 95% CI, 1.47-2.41), but there was no interaction between parental atopy and pet exposure. CONCLUSIONS: The present results are consistent with the hypothesis that both keeping furry pets and parental atopy increase the risk of asthma development in adulthood. Parental atopy does not modify the effects of pet exposure. The negative association between current pets and the risk of asthma is consistent with selective avoidance of these pets by symptomatic individuals.     

A novel missense mutation in exon 3 of the COL4A5 gene associated with late-onset Alport syndrome

We have identified a novel missense transition (362G→A) in exon 3 of the COL4A5 gene in a male patient with late-onset Alport syndrome. We used non-isotopic single strand conformation polymorphism, heteroduplex analysis, and automated DNA sequencing. The mutation changes a conserved glycine at codon 54 for an aspartic acid (Gly54Asp), which abolishes a BstNI site. Using restriction analysis, we identified the heterozygous carrier status in the two daughters of the proband. Our findings are in keeping with the hypothesis that slower progressive forms of Alport syndrome are more often associated with missense mutations rather than large deletions or frameshifts. This is the first mutation described in the N-terminus triple helical 7S domain of the COL4A5 gene in an Alport syndrome patient.     

Long-lasting heterologous antibody responses after sequential vaccination with A/Indonesia/5/2005 and A/Vietnam/1203/2004 pre-pandemic influenza A(H5N1) virus vaccines

BackgroundAvian influenza A(H5N1) viruses have caused sporadic infections in humans and thus they pose a significant global health threat. Among symptomatic patients the case fatality rate has been ca. 50%. H5N1 viruses exist in multiple clades and subclades and several candidate vaccines have been developed to prevent A(H5N1) infection as a principal measure for preventing the disease.MethodsSerum antibodies against various influenza A(H5N1) clade viruses were measured in adults by ELISA-based microneutralization and haemagglutination inhibition tests before and after vaccination with two different A(H5N1) vaccines in 2009 and 2011.ResultsTwo doses of AS03-adjuvanted A/Indonesia/5/2005 vaccine induced good homologous but poor heterologous neutralizing antibody responses against different clade viruses. However, non-adjuvanted A/Vietnam/1203/2004 booster vaccination in 2011 induced very strong and long-lasting homologous and heterologous antibody responses while homologous response remained weak in naïve subjects.ConclusionsSequential vaccination with two different A(H5N1) pre-pandemic vaccines induced long-lasting high level cross-clade immunity against influenza A(H5N1) strains, thus supporting a prime-boost vaccination strategy in pandemic preparedness plans.